Fluoride (F) readily traverses cell membranes and cell layers (e.g., epithelia of the gastrointestinal tract), and this transfer is considered to occur by passive diffusion. The pH dependence of F transfer has led to the proposal that the permeable species is undissociated HF, and that cell membranes are essentially impermeable to fluoride ion F-. This has been demonstrated in bacteria and cell suspensions. An increase in F transfer in response to a lowering of pH has also been shown in renal excretion and in F absorption in the stomach and the urinary bladder. Absorption of F occurs very readily in the small intestine despite the high pH and hence extremely low HF concentration, and the pH dependence of intestinal F absorption has not been subjected to rigorous analysis. This proposal is directed toward the question: Is F transfer across the small intestine directly proportional to undissociated HF concentration? Segments of wall of the small intestine of dogs will be mounted as flat sheets in a two-chamber incubation apparatus, and the transfer of F from the mucosal to the serosal side measured under varying conditions of total E concentration and pH. This is vitro system will be used because it avoids the complexities of whole animal absorption studies and permits precise control of pH and of total F, undissociated HF and fluoride ion F- concentrations. The HF concentration can be calculated under any conditions of pH and total F concentration from the Henderson-Hasselbalch equation. By systematically varying pH and total F concentration, the concentration of undissociated HF can be held constant over a wide range of total F concentration. In addition, the HF and F- concentrations can be manipulated so that they both increase or decrease together, or one may increase while the other decreases. By manipulating the F concentrations and pH on the mucosal side and measuring the rate of F accumulation on the serosal side, the relationship between F transfer and concentrations of the different F species can be investigated.